Overview of and approach to the idiopathic inflammatory myopathies

INTRODUCTION — The idiopathic inflammatory myopathies (IIMs) include dermatomyositis (DM), polymyositis (PM), myositis as part of a rheumatic disease overlap syndrome, myositis of the antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). These diseases share the clinical manifestation of progressive muscle weakness and the histopathologic finding of inflammatory infiltrates of varying degrees in muscle tissue. Variations in extramuscular clinical manifestations, specific findings on muscle biopsy, and disease-specific serologic abnormalities help to distinguish one of these entities from another.

Although much is known about the pathologic processes present in this group of diseases, the precise cause of the IIMs remains unknown. (See "Pathogenesis of inflammatory myopathies".)

The nomenclature and classification criteria of the IIMs will be addressed in this topic, as well as a general approach to the diagnosis, differential diagnosis, and treatment of the IIMs. A more complete and detailed description of clinical manifestations, laboratory findings, and treatment options in the various IIMs are discussed in separate topics. (See "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Initial treatment of dermatomyositis and polymyositis in adults" and "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults" and "Clinical manifestations and diagnosis of inclusion body myositis" and "Management of inclusion body myositis".)

NOMENCLATURE — Some authors use "immune-mediated myopathy" (IMM) instead of "idiopathic inflammatory myopathy" (IIM) to describe this group of diseases because in some cases, such as statin-induced necrotizing myopathy, there is little if any inflammatory cell infiltrate [1].

Polymyositis (PM) is thought to be quite rare. In the last decade, the concept of pure PM has been absorbed by separate defined entities, including immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM) that is early in diagnosis or misdiagnosed, or myositis secondary to a connective tissue disease overlap syndrome. Additionally, antisynthetase syndrome may present with a myopathy without a rash; some experts would classify this as PM whereas others prefer to recognize the antisynthetase syndrome as a separate entity.

Overlap syndrome refers to the coexistence of inflammatory myopathy with another systemic rheumatic disease such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), mixed connective tissue disease (MCTD), and, less often, rheumatoid arthritis (RA) and Sjögren's disease.

Antisynthetase syndrome is defined by the presence of inflammatory myopathy and/or extramuscular manifestations affecting skin, lung, or joints together with an antibody directed against an aminoacyl-transfer ribonucleic acid (tRNA) synthetase. Myositis may not always be present when interstitial lung disease and/or arthritis are prominent feature(s).

MAJOR DISEASE SUBTYPES — Brief descriptions of the various disorders classified as idiopathic inflammatory myopathies (IIMs) will be presented here. More detailed information can be found in the specific disease topics.

Dermatomyositis — Patients with classic dermatomyositis (DM) typically present with symmetric muscle weakness, elevated muscle enzymes, and characteristic cutaneous findings. Antinuclear antibodies (ANAs) may be present, including in patients with a DM-specific autoantibody, such as anti-Mi-2, anti-NXP2, anti-transcriptional intermediary factor 1gamma (anti-TIF 1gamma), or anti-small ubiquitin-like modifier activating enzyme (anti-SAE). By contrast, another DM-specific antibody, anti-melanoma differentiation-associated gene 5 (anti-MDA5), is cytoplasmic in origin. Myositis-specific antibodies are detected in 45 to 85 percent of adult patients with IIM depending on the test and laboratory utilized [2]. Many experts use the presence of a myositis-specific antibody to determine what particular myositis phenotype a patient may have, and thereby to help with prognostication, rather than to make the diagnosis of DM. As an example, the presence of anti-TIF-1gamma is associated with an increased risk of cancer in these patients. (See "Malignancy in dermatomyositis and polymyositis" and "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Clinically amyopathic dermatomyositis — Patients with clinically amyopathic DM (CADM) are those patients with cutaneous findings who lack clinical evidence of muscle involvement (see "Cutaneous dermatomyositis in adults: Overview and initial management"). Patients are considered to have provisional CADM at six months and confirmed CADM at two years. Despite lacking clinically significant muscle disease, concomitant pulmonary disease or malignancy may still occur, thus mandating appropriate workup. A subset of these patients, those with "hypomyopathic dermatomyositis," will have minimal elevations of muscle enzymes or subtle abnormalities on muscle studies in the absence of any objective or subjective weakness. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Diagnosis'.)

Similar to patients with classic DM, some CADM patients will have myositis-specific antibodies. As described above, these are typically used by experts more for prognostication than for diagnosis. As an example, the presence of anti-MDA5 is associated with an increased likelihood of amyopathic disease as well as an increased risk of interstitial lung disease. (See 'Myositis-specific autoantibodies' below.)

Polymyositis — Patients presenting with weakness and elevated muscle enzymes in the absence of characteristic cutaneous findings of DM present a more difficult diagnostic challenge as there are no specific cutaneous findings of other IIMs and diagnostic serologic tests are less likely to be present. Most importantly, these patients need to be distinguished from other causes of myopathy without rash including hypothyroid myopathy, the various forms of muscular dystrophy, and metabolic myopathies. All patients presenting with evidence of myopathy without rash should be screened for hypothyroidism with appropriate thyroid function testing. Additionally, patients with immune-mediated necrotizing myopathy (IMNM) and inclusion body myositis (IBM) present with muscle disease without rash and may be difficult to distinguish from primary polymyositis (PM), and care must be taken to avoid misclassification as PM cases. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Overlap syndromes — Inflammatory myopathy may occur in the setting of another systemic rheumatic disease such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), mixed connective tissue disease (MCTD), and, less often, rheumatoid arthritis (RA) and Sjögren's disease. The muscle involvement is often subclinical or mild. Mild elevations of creatine kinase may occur and be the only indication of muscle involvement. Certain autoantibodies have been associated with overlap syndromes. As an example, MCTD is defined by the presence of the anti-ribonucleoprotein (RNP) antibody and the presence of overlapping clinical features of inflammatory myopathy, SLE, and/or SSc (see "Mixed connective tissue disease"). Patients with the anti-PM-Scl antibody manifest various degrees of myositis along with telangiectasias, Raynaud phenomenon, "mechanic's hands," inflammatory arthritis, and SSc. (See "Neuromuscular manifestations of systemic sclerosis (scleroderma)", section on 'Laboratory testing'.)

Antisynthetase syndrome — Antisynthetase syndrome group is defined by the presence of an antibody directed against one of several aminoacyl-transfer RNA (tRNA) synthetases. Clinical findings include inflammatory myopathy and extramuscular findings including interstitial lung disease, "mechanic's hands" (picture 1), inflammatory arthritis, and Raynaud phenomenon. Onset is often more acute than in primary DM. There does not appear to be an increased risk of malignancy in this group.

Immune-mediated necrotizing myopathy — Clinically, this group resembles primary PM, but the extent of muscle necrosis and relative paucity of inflammatory infiltrate seen on muscle biopsy distinguish it from PM. One subgroup with this myopathy has associated anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) autoantibodies with or without a history of statin use. Another subgroup has associated autoantibodies to the signal recognition particle (SRP).

Inclusion body myositis — Although classified with the IIMs, IBM has epidemiologic, clinical, and histopathologic findings that distinguish it from the other IIMs. IBM affects older individuals, more commonly men. It generally has a more insidious onset and slower progression than the other inflammatory myopathies. The distribution of weakness tends to be more distal in the upper extremities and less symmetric. Autoantibodies against cytosolic 5'-nucleotidase 1A (NT5C1A) are present in the sera in approximately half of patients [3,4]. Muscle biopsy shows prominent endomysial inflammatory infiltrate and muscle fibers with rimmed vacuoles and inclusions. However, rimmed vacuoles and inclusions are not evident in 20 to 30 percent of any given muscle biopsy, suggesting the need for repeated biopsy in selected patients [5,6]. Pathogenesis is not understood but is likely distinct from the other IIMs. (See "Clinical manifestations and diagnosis of inclusion body myositis" and "Pathogenesis of inflammatory myopathies".)

DIAGNOSTIC APPROACH — The most common presentation of patients with idiopathic inflammatory myopathy (IIM) is gradual onset of symmetric proximal muscle weakness associated with enzyme elevations indicative of muscle injury due to inflammation, namely an elevation of creatine kinase and other muscle enzymes (see "Approach to the patient with muscle weakness" and "Muscle enzymes in the evaluation of neuromuscular diseases"). However, the clinician needs to recognize the possibility of an IIM even in patients without evidence of muscle weakness and also needs to recognize the clinical, laboratory, and histopathologic findings that distinguish the different diseases classified as IIM. Furthermore, not all patients with myopathy will have elevated creatine kinase or other muscle enzyme levels, thus requiring other muscle studies to confirm the diagnosis.

Clinical presentation — We recognize three distinct clinical presentations of IIM:

●Patients presenting with evidence of muscle weakness only. Patients usually report a history of the insidious or subacute development of the muscle weakness, with gradual worsening over a period of several months before medical attention is sought, which helps to distinguish IIM from the many causes of rhabdomyolysis (see "Rhabdomyolysis: Epidemiology and etiology"), which is usually very sudden in onset. Patients may describe increasing difficulty climbing stairs, getting up from a chair, carrying heavy groceries, or picking up their children due to the proximal muscle involvement. Primary polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) would fall into this category.

●Patients presenting with evidence of extramuscular disease only. Pathognomonic or characteristic cutaneous eruptions, pulmonary disease, inflammatory arthritis, and Raynaud phenomenon may be the presenting features of an IIM. Dermatologic manifestations are highly variable and include Gottron papule and Gottron sign, pink to violaceous erythema of the eyelids (referred to as the heliotrope eruption), midfacial erythema involving the nasolabial folds, periungual erythema and nailfold capillary abnormalities, poikiloderma of sun-exposed areas including the "shawl" and "V-neck" signs, scalp erythema and psoriasiform scaling, "holster" sign, and calcinosis cutis, among many others. Hyperkeratotic, fissured skin on the palmar and lateral aspects of the fingers, termed "mechanic's hands," is characteristic of antisynthetase syndrome (see "Cutaneous dermatomyositis in adults: Overview and initial management"). Pulmonary disease includes various forms of interstitial lung disease. When present, inflammatory arthritis resembles rheumatoid arthritis (RA). Patients may have a constellation of extramuscular manifestations such as skin rash in combination with interstitial lung disease. Patients with cutaneous dermatomyositis (DM) in the absence of muscle involvement are referred to as having CADM.

●Patients presenting with both muscle disease and extramuscular manifestations. This presentation would include patients with classic DM, who have both typical DM skin disease and muscle weakness, patients with antisynthetase syndrome, and patients with overlap conditions. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Laboratory findings — Laboratory abnormalities in IIM include nonspecific abnormalities indicative of muscle inflammation or systemic illness or specific serologic abnormalities characteristic of specific IIM subgroups.

Muscle enzymes — Most patients with IIM will have an elevation of one or more of the muscle-derived enzymes, creatine kinase, lactate dehydrogenase (LDH), aldolase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Creatine kinase is the most sensitive muscle enzyme and is the one most commonly tested for and followed. Creatine kinase levels vary widely but are often increased more than 10-fold above the upper limit of normal (ULN) in untreated disease. However, creatine kinase levels can be normal in 20 percent of patients with DM, even in those patients with weakness and active muscle inflammation on studies, and are often normal or only slightly elevated in IBM (ie, less than 10 times the ULN) [7]. Creatine kinase levels can be used to follow the response to treatment and to detect disease relapse in most patients, but the levels do not correlate with disease severity. (See "Muscle enzymes in the evaluation of neuromuscular diseases".)

While creatine kinase levels in the inflammatory myopathies may be extremely high, even in the range seen in acute rhabdomyolysis, the complication of acute rhabdomyolysis with its risk of acute renal injury is rarely seen with the IIM diseases.

It should be noted that not all elevations of AST and ALT are evidence of liver disease, especially when AST is higher than ALT. Patients with an unexplained elevation of transaminases should have a creatine kinase level checked to evaluate for evidence of myopathy in order to avoid an unnecessary liver biopsy.

Myositis-specific autoantibodies — Myositis-specific autoantibodies are associated with particular clinical syndromes within the IIM spectrum. The evaluation of patients suspected of having an IIM is facilitated by serologic test panels available from reference laboratories. This eliminates the need to order the numerous tests individually. However, the results are often not available for several weeks, while treatment decisions may need to be made before the specific serologic profile is known. Furthermore, given that these tests are only positive in 20 to 40 percent of patients (depending on the specific disease), a negative myositis panel does not rule out a diagnosis of myositis. In fact, many experts use the myositis panel to determine what particular myositis phenotype may best fit the patient rather than to make a diagnosis of myositis. Notably, many commercially available myositis panels have varying degrees of accuracy. Hence, using careful clinical judgment based on the patient's examination and studies is crucial.

●Antisynthetase antibodies – This family of antibodies is directed against aminoacyl-transfer RNA (tRNA) synthetases. For example, the anti-Jo-1 antibody is directed against histidyl-tRNA synthetase. Anti-Jo-1 is the most common antisynthetase antibody and the most common myositis-specific autoantibody, occurring in approximately 20 percent of IIM patients. These antibodies are strongly associated with interstitial lung disease, Raynaud phenomenon, arthritis, and mechanic's hands (picture 1) [8].

Anti-Jo-1 and other antisynthetase antibodies, such as anti-PL-12, have been observed in some patients with interstitial lung disease who lack evidence of myositis [9]. Other antisynthetase antibodies include antibodies to the OJ, EJ, PL-7, PL-12, KS, Zo, and Ha antigens [10-12]. In the aggregate, these other antisynthetases are found in 1 to 5 percent of IIM patients. Patients with these may have clinical manifestations similar to those with anti-Jo-1-antibodies, but differences have sometimes been noted, particularly in the frequency of myositis [9]. Individual patients with antisynthetase syndrome usually have an antibody to only one unique synthetase.

●Anti-SRP antibody – The signal recognition particle (SRP) is involved in the translocation of newly synthesized proteins into the endoplasmic reticulum. Anti-SRP antibodies have been found in approximately 5 percent of patients with IIM [13,14]. Muscle biopsies in these patients show a necrotizing myopathy with minimal inflammation, and extramuscular manifestations are infrequent. These patients tend to have severe disease with marked weakness and very high creatine kinase levels. Disease activity is often difficult to control completely even with appropriate immunosuppressive treatment [15,16].

Anti-SRP antibodies are highly specific for IMNM; however, they have been described in two patients with limb girdle muscular dystrophy and two patients with systemic sclerosis (SSc; scleroderma), in a patient with antisynthetase syndrome without myopathy, and in several patients with rashes typical of DM [15,17,18].

●Anti-Mi-2 antibody – Anti-Mi-2 antibodies are directed against a helicase involved in transcriptional activation [19]. They are associated with the relatively acute onset of DM, are traditionally associated with a classic shawl or V-sign, and may respond well to therapy [20]. Patients with anti-Mi2-positive DM tend to have more severe muscle disease than patients with DM in the absence of Mi2 autoantibodies or patients with antisynthetase syndrome. Anti-Mi2 autoantibody levels appear to correlate with disease severity and may normalize with clinical remission [21]. In addition, in some studies, DM patients with anti-Mi-2 antibodies appear to have a lower risk of associated malignancy [22,23].

●Anti-MDA5 antibody – These antibodies recognize the RNA helicase encoded by the melanoma differentiation-associated gene 5 (MDA5), a protein involved in the innate immune response. Initially, anti-MDA5 antibody was reported as a particular autoantibody for clinically amyopathic DM (CADM) and was referred to as anti-CADM-140; the target autoantigen was later recognized as gene 5 linked with melanoma differentiation (MDA5) [22]. The presence of anti-MDA5 is strongly associated with interstitial lung disease, including a rapidly progressive phenotype with high morbidity and mortality (see "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis"). Patients with MDA5 DM tend to lack muscle involvement but often have arthritis [24,25]. In addition, there is a characteristic cutaneous phenotype that includes ulcerations over the Gottron papules and sign, painful palmar papules and macules, oral ulcerations, and nonscarring alopecia [24,26-30].

●Anti-NXP-2 antibody – This autoantibody against nuclear matrix protein 2 (NXP-2), which has a role in transcriptional regulation, was previously referred to as anti-MJ or anti-p140. It is associated with juvenile or young-onset DM with severe disease, edema, and calcinosis. This antibody may be associated with malignancy in adults, particularly in males [31]. In addition, this antibody can also be associated with prominent muscle disease, dysphagia, myalgia, and calcinosis in adults and has been found in 11 to 24 percent of DM patients [11,12,32-34].

●Anti-TIF-1gamma antibody – This myositis-specific autoantibody, previously known as the anti-p155/140 antibody, has reactivity with the 155-kD nuclear protein transcriptional intermediary factor (TIF) 1gamma and often also with the 140-kD TIF-1alpha [12,35,36]. This autoantibody is associated with a characteristic cutaneous phenotype including palmar hyperkeratotic papules, psoriasis-like lesions, and hypopigmented and telangiectatic "red-on-white" patches [37]. Furthermore, it is also strongly associated with an increased risk of cancer [31,38-41]. Another associated clinical feature is the ovoid palatal patch, which is strongly correlated with malignancy. (See "Malignancy in dermatomyositis and polymyositis", section on 'Serum autoantibodies'.)

●Anti-SAE antibody – These autoantibodies target the small ubiquitin-like modifier activating enzyme (SAE) that regulates gene transcription. Anti-SAE autoantibodies have been detected in 5 to 10 percent of patients with DM [42]. Patients are described as having a high prevalence of dysphagia and cutaneous manifestations that precede the development of myopathy [43]. These patients are sometimes thought initially to have CADM but may then go on to develop severe myositis and may have an increased risk for malignancy [29,41].

●Anti-HMGCR antibody – The antigen for this autoantibody is 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a key enzyme in cholesterol synthesis. Patients with anti-HMGCR develop an IMNM with little inflammatory infiltrate similar to patients with anti-SRP antibody. Anti-HMGCR is also associated with statin use, although up to 50 percent of patients with this antibody are statin naïve [44,45]. (See "Statin muscle-related adverse events".)

Myositis-associated autoantibodies — Myositis-associated autoantibodies are those found in patients with other systemic rheumatic diseases that can be associated with myositis.

The detection of anti-Ro/SSA, anti-La/SSB, anti-Sm, or anti-ribonucleoprotein (RNP) antibodies in a patient with myositis suggests association or overlap with another systemic rheumatic disease. Anti-Ro52 antibodies are common in patients with antisynthetase antibodies, and anti-Ro60 and anti-La/SSB may be seen in a smaller number of such patients and in those with other myositis-specific antibodies. Anti-Ro/SSA and occasionally anti-La/SSB can be seen in up to one-fifth of those with IBM but often may not have any associated clinical features of Sjögren's disease [46]. (See "The anti-Ro/SSA and anti-La/SSB antigen-antibody systems" and "Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP".)

Anti-PM-Scl and anti-Ku antibodies have been identified in patients with overlapping features of myositis and SSc [47]. Many patients with these antibodies, however, do not have myositis [48]. (See "Neuromuscular manifestations of systemic sclerosis (scleroderma)", section on 'Laboratory testing'.)

Other — Some patients with IIM will have an anemia of chronic disease. Markers of systemic inflammation such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are not uniformly elevated in IIM.

While antinuclear antibodies (ANAs) detected by standard immunofluorescence methods may be present in up to 60 percent of patients with DM or PM, ANA testing is not diagnostic for DM or PM [49].

Additional diagnostic studies

Electromyography — Electromyography (EMG) can identify myopathic changes that help to distinguish myopathy from neuropathic causes of motor weakness such as motor neuron disease, peripheral polyneuropathy, or myasthenia gravis. It is also useful in identifying muscle involvement in patients with mild or equivocal weakness or in patients with extramuscular manifestations of IIM but no objective weakness. Characteristic abnormalities on EMG (eg, presence of fibrillation potentials) can support a diagnosis of IIM but are not diagnostic of it, as similar findings occur in various infectious, toxic, or metabolic myopathies. EMG can be used to identify the muscle group that is likely to provide useful information on biopsy, but muscle biopsy should not be performed on a muscle that has recently undergone EMG testing. (See "Overview of electromyography".)

Skeletal muscle imaging — Magnetic resonance imaging (MRI) can demonstrate areas of muscle inflammation, edema with active myositis, fibrosis, and calcification (image 1). Unlike muscle biopsy, MRI can assess large areas of muscle (eg, both thighs), thereby avoiding problems with sampling error. It is, however, nonspecific and may not distinguish the changes of IIM from those that occur in rhabdomyolysis, muscular dystrophy, or metabolic myopathy.

Musculoskeletal ultrasound is a less expensive and less time-consuming technology than MRI, but there is not as much experience with ultrasound as MRI, and skeletal muscle ultrasound remains operator dependent.

Muscle and skin biopsy — Muscle biopsy should be performed in patients presenting with clinical and/or laboratory evidence of myopathy who do not have extramuscular manifestations such as a typical DM rash or a myositis-specific autoantibody. In the absence of these more specific findings, PM may not be distinguishable from IMNM or other forms of myopathy such as muscular dystrophy or a metabolic myopathy. Muscle biopsy may not be necessary in every patient suspected of an IIM if the diagnosis can be established on the basis of clinical and laboratory findings.

Although all of the IIMs share variable degrees of histologic features that include muscle fiber necrosis, degeneration, regeneration, and an inflammatory cell infiltrate, certain characteristic findings help to distinguish the disorders from each other and reflect their distinct pathophysiologic pathways (see "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Muscle histopathology' and "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis"). For example, the pathologic changes in muscle in DM tend to be vascular, located in the perifascicular region of the muscle, while in PM, the cellular infiltrate is predominantly within the fascicle, with inflammatory cells invading individual muscle fibers. The presence of prominent necrosis together with a paucity of inflammatory cells is typical of IMNM, while the presence of rimmed vacuoles and Congo red or p62+ inclusions or tubulofilament-filled inclusions on electron microscopy are characteristic of IBM.

Although clinical and serologic findings may be diagnostic in some patients, others may present with ambiguous cutaneous findings or cutaneous findings that are suggestive of DM in the absence of clinical signs of muscle disease. In these cases, a skin biopsy may be helpful. The skin biopsy of DM cannot be distinguished from that of lupus erythematosus (LE) but is distinctive from many other mimickers such as atopic dermatitis, psoriasis, and seborrheic dermatitis. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Skin biopsy'.)

CLASSIFICATION CRITERIA — Classification criteria are established to provide uniformity of subjects in clinical trials. Although their imperfect sensitivity and specificity limit their use for diagnostic purposes in individual patients, these criteria are helpful to clinicians in identifying key features of the diseases. Several sets of classification criteria have been developed for idiopathic inflammatory myopathies (IIMs) for the primary purpose of defining these disorders for clinical and epidemiologic research.

In 2017, the European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) and the American College of Rheumatology (ACR) developed and validated revised classification criteria for adult and juvenile IIMs and their major subgroups [50,51]. These criteria address some of the shortcomings of previously used classification systems by capturing a broader spectrum of patients and subgroups with IIM, and by including more well-defined clinical and laboratory criteria [52-57]. The criteria were derived from data on 976 IIM patients (74 percent adults; 26 percent children) and 624 non-IIM patients with mimicking conditions (82 percent adults; 18 percent children).

The EULAR/ACR criteria classify patients as having "definite," "probable," and "possible" disease based on a score and corresponding probability of disease. The ACR/EULAR approach identifies 16 distinct clinical, serologic, and muscle biopsy variables which can be entered into a web-based calculator. With this approach, sensitivity and specificity for correctly identifying cases of probable IIM are 93 and 88 percent, respectively. However, there were not sufficient cases in their study cohort for the calculator to be able to identify the more rare subgroups such as immune-mediated necrotizing myopathy (IMNM) or antisynthetase syndrome.

A classification tree for the subgroups of IIM is also provided by the criteria to help distinguish adult from juvenile IIM and then subclassify adult patients into polymyositis (PM), dermatomyositis (DM), clinically amyopathic DM (CADM), or inclusion body myositis (IBM). In addition, adult patients with pathognomonic skin eruptions (heliotrope eruption and/or Gottron papules and/or Gottron sign) are classified with DM without including muscle biopsy data. A muscle biopsy, however, is recommended for patients without the cutaneous manifestations. In these guidelines, a skin biopsy is recommended for DM patients without muscle involvement.

Prior to this, the most widely used classification criteria developed by Bohan and Peter in 1975 defined DM and PM based upon the following features [53,54]:

●Symmetric proximal muscle weakness

●Typical cutaneous eruption of DM (the only feature distinguishing DM from PM)

●Elevated serum muscle enzymes

●Myopathic changes on electromyography (EMG)

●Characteristic muscle biopsy abnormalities and the absence of histopathologic signs of other myopathies

Patients with the cutaneous eruption and at least three of the other four criteria met the requirements for definite DM according to these criteria, while requirements for definite PM were met by those with all four criteria other than the cutaneous features [53]. Patients with findings indicating the presence of other disorders that may present similarly were excluded. Patients who did not meet these criteria but who lacked any of the exclusions could potentially have been diagnosed with possible or probable DM or PM, depending upon the number of criteria met.

Several sets of classification criteria have also been proposed for amyopathic DM [55,58,59]. Dermatology experts have suggested the following criteria for amyopathic DM [58,59]:

●Biopsy-confirmed hallmark cutaneous manifestations of classic DM occurring for six months or longer.

●No clinical evidence of proximal muscle weakness and no serum muscle enzyme abnormalities for six months or longer.

●If more extensive muscle testing is carried out, the results are within normal limits.

●Absence of exclusion criteria. Exclusion criteria include treatment with systemic immunosuppressive therapy for two consecutive months or longer within the first six months after skin disease onset or use of drugs known to be capable of producing DM-like skin changes (eg, hydroxyurea, statins, etc) at the onset of cutaneous DM changes.

Similar criteria for amyopathic DM, but which also included electrophysiologic studies, were proposed by an expert group of neurologists and rheumatologists [55]. These included:

●Rash typical of DM (eg, heliotrope, periorbital edema, Gottron papules, Gottron sign, V-sign, shawl sign, holster sign)

●Skin biopsy that demonstrates a reduced capillary density, deposition of complement membrane attack complex (MAC) on small blood vessels along the dermal-epidermal junction, and variable keratinocyte decoration for MAC

●No objective weakness, normal creatine kinase, and normal EMG

●Muscle biopsy, if done, that does not reveal features compatible with definite or probable DM

DIFFERENTIAL DIAGNOSIS — The idiopathic inflammatory myopathies (IIMs) must be distinguished from other conditions that cause muscle weakness, with or without elevated muscle enzymes. The differential diagnosis thus includes infectious and drug-induced myopathies, sarcoid myopathy, amyloid myopathy, hypothyroid myopathy, muscular dystrophy, inherited metabolic myopathies, motor neuron disease, myasthenia gravis, and myositis caused by graft-versus-host disease. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Differential diagnosis'.)

The IIMs share some clinical and pathologic manifestations with, and need to be distinguished from, known causes of myopathy including infectious (see "Overview of viral myositis"), drug (see "Drug-induced myopathies"), and metabolic causes. (See "Approach to the metabolic myopathies".)

Polymyalgia rheumatica and fibromyalgia should not be confused with the IIMs despite their nomenclature. These conditions are not muscle diseases, and muscle pain rather than true muscle weakness is their predominant symptom. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica" and "Clinical manifestations and diagnosis of fibromyalgia in adults".)

The skin findings in dermatomyositis (DM) may be difficult to distinguish from multiple other cutaneous eruptions, including lupus erythematosus (LE), psoriasis, atopic dermatitis, and seborrheic dermatitis, among others (see "Overview of cutaneous lupus erythematosus" and "Psoriasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Seborrheic dermatitis in adolescents and adults"). Fortunately, skin biopsy can distinguish the rash of DM from all of these entities except for LE. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Skin biopsy'.)

MANAGEMENT — The management of idiopathic inflammatory myopathies (IIMs) depends in part on the specific IIM subgroup. For example, inclusion body myositis (IBM) is generally unresponsive to antiinflammatory or immunosuppressive treatment, while the other forms of IIM with greater degrees of muscle inflammation are generally responsive. Treatment also needs to be individualized depending on the severity of weakness, disease duration, presence of extramuscular manifestations, presence of an underlying malignancy, age of patient, and comorbidities. Detailed information regarding treatment can be found in separate topic reviews. (See "Initial treatment of dermatomyositis and polymyositis in adults" and "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults" and "Management of inclusion body myositis" and "Cutaneous dermatomyositis in adults: Overview and initial management" and "Management of refractory cutaneous dermatomyositis in adults".)

With the exception of IBM, the initial mainstay of therapy of active myositis is glucocorticoids in conjunction with a glucocorticoid-sparing agent. Examples of glucocorticoid-sparing agents include methotrexate, mycophenolate, azathioprine, and rituximab, which are used for longer-term treatment. Intravenous immune globulin (IVIG) may hasten response to treatment, which is important in patients with severe disease with marked weakness or dysphagia. Physical therapy, measures to prevent aspiration in patients with esophageal dysmotility, and glucocorticoid-induced osteoporosis prevention are important general measures.

For patients with DM and skin findings, the therapeutic ladder can differ from that targeting muscle disease. Management considerations include photoprotection and antimalarial drugs; however, many patients with DM skin disease require additional immunosuppressive or immunomodulatory agents for adequate disease control. (See "Cutaneous dermatomyositis in adults: Overview and initial management" and "Management of refractory cutaneous dermatomyositis in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dermatomyositis and polymyositis".)

SUMMARY

●Major disease subtypes – The idiopathic inflammatory myopathies (IIMs) in adults include dermatomyositis (DM), clinically amyopathic DM (CADM), polymyositis (PM), overlap syndromes, antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Of note, the concept of PM has evolved and is less frequent than originally thought, as it had likely previously encompassed unrecognized IMNM, IBM, and antisynthetase syndrome (in the absence of rash). (See 'Major disease subtypes' above and 'Nomenclature' above.)

●Clinical presentation – An IIM should be considered in patients presenting with muscle weakness, most commonly gradual-onset symmetric proximal muscle weakness. Most patients will also have elevated muscle enzymes, with creatine kinase the most sensitive and most commonly tested enzyme. (See 'Clinical presentation' above.)

Extramuscular presentations include a variety of cutaneous manifestations, interstitial lung disease, rheumatoid arthritis (RA), or Raynaud phenomenon. Features of overlap syndromes may also be present, such as findings of systemic lupus erythematosus (SLE) or systemic sclerosis (SSc; scleroderma). Patients with CADM and some with antisynthetase syndrome will present with only extramuscular manifestations and no evidence of muscle involvement. (See 'Clinical presentation' above.)

●Laboratory findings – Muscle enzymes should be obtained to aid with diagnosis. A panel of myositis-specific and myositis-associated antibodies may also be helpful, although there is wide variation in test reliability across various laboratory platforms. (See 'Laboratory findings' above.)

●Additional diagnostic studies – Additional diagnostic studies to help identify myopathy include electromyography (EMG), skeletal muscle imaging with MRI, typically of the bilateral thighs, as well as muscle and skin biopsy. (See 'Additional diagnostic studies' above.)

●Differential diagnosis – IIM needs to be differentiated from other causes of proximal muscle weakness and rash, including hypothyroid myopathy, muscular dystrophies, metabolic myopathies, drug-induced myopathy, and SLE, among others. (See 'Differential diagnosis' above.)

●Management – Treatment of IIM depends on the specific subgroup of IIM and should be individualized for the specific patient. Initial treatment usually includes glucocorticoids and glucocorticoid-sparing agents to suppress muscle inflammation and restore strength. Commonly used agents for IIM include methotrexate, mycophenolate, azathioprine, intravenous immune globulin (IVIG), and rituximab, among others. Skin disease in DM may warrant a different therapeutic approach than that typically utilized to target muscle disease. (See 'Management' above and "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Treatment'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc L Miller, MD, who contributed to an earlier version of this topic review.